Chemical pollution in the environment is supersizing the global obesity epidemic, according to a major scientific review.
The idea that the toxins called “obesogens” can affect how the body controls weight is not yet part of mainstream medicine. But the dozens of scientists behind the review argue that the evidence is now so strong that it should be. “This is critical because the current clinical management of obese patients is woefully inadequate,” they said.
The most disturbing aspect of the evidence is that some chemical impacts that increase weight can be passed down through generations by changing how genes work. Pollutants cited by the researchers as increasing obesity include bisphenol A (BPA), which is widely added to plastics, as well as some pesticides, flame retardants and air pollution.
Global obesity has tripled since 1975, with more people now obese or overweight than underweight, and is increasing in every country studied. Almost 2 billion adults are now too heavy and 40 million children under five are obese or overweight.
“The focus of the clinical people is on calories – if you eat more calories, you’re going to be more fat,” says Dr Jerrold Heindel, lead author of one of the three review papers, and formerly at the US National Institute of Environmental Health Sciences. “So they wait untill you get obese, then they’ll look at giving you diets, drugs, or surgery.
“If that really worked, we should see a decline in the rates of obesity,” he said. “But we don’t – obesity continues to rise, especially in children. The real question is, why do people eat more? The obesogenic paradigm focuses on that and provides data that indicate that these chemicals are what can do that.”
Furthermore, the scientists say, the approach offers the potential to prevent obesity by avoiding exposure to pollutants, especially in pregnant women and babies: “Prevention saves lives, while costing far less than any [treatment].”
Strong evidence
The evidence for obesogens is set out by more than 40 scientists in three review papers, published in the peer-reviewed journal Biochemical Pharmacology and citing 1,400 studies. They say these chemicals are everywhere: in water and dust, food packaging, personal hygiene products and household cleaners, furniture and electronics.
The review identifies about 50 chemicals as having good evidence of obesogenic effects, from experiments on human cells and animals, and epidemiological studies of people. These include BPA and phthalates, also a plastic additive. A 2020 analysis of 15 studies found a significant link between BPA levels and obesity in adults in 12 of them.
Other obesogens are pesticides, including DDT and tributyltin, former flame retardants and their newer replacements, dioxins and PCBs, and air pollution. Several recent studies link exposure to dirty air early in life to obesity.
The review also names PFAS compounds – so-called “forever chemicals” due to their longevity in the environment – as obesogens. These are found in food packaging, cookware, and furniture, including some child car seats. A two-year, randomised clinical trial published in 2018 found people with the highest PFAS levels regained more weight after dieting, especially women.
Some antidepressants are also well known to cause weight gain. “That is a proof of principle that chemicals made for one thing can have side effects that interfere with your metabolism,” said Heindel. Other chemicals with some evidence of being obesogens included some artificial sweeteners and triclosan, an antibacterial agent banned from some uses in the US in 2017.
How it works
Obesogens work by upsetting the body’s “metabolic thermostat”, the researchers said, making gaining weight easier and losing weight harder. The body’s balance of energy intake and expenditure through activity relies on the interplay of various hormones from fat tissue, the gut, pancreas, liver, and brain.
The pollutants can directly affect the number and size of fat cells, alter the signals that make people feel full, change thyroid function and the dopamine reward system, the scientists said. They can also affect the microbiome in the gut and cause weight gain by making the uptake of calories from the intestines more efficient.
“It turns out chemicals dumped in the environment have these side effects, because they make the cells do things that they wouldn’t otherwise have done, and one of those things is laying down fat,” said Prof Robert Lustig at the University of California, San Francisco, and lead author of another of the reviews.
The early years of child development are the most vulnerable to obesogens, the researchers wrote: “Studies showed that in utero and early-life exposures were the most sensitive times, because this irreversibly altered programming of various parts of the metabolic system, increasing susceptibility for weight gain.”
“We’ve got four or five chemicals that also will cause transgenerational epigenetic obesity,” said Heindel, referring to changes in the expression of genes that can be inherited. A 2021 study found that women’s level of obesity significantly correlated with their grandmothers’ level of exposure to DDT, even though their granddaughters were never directly exposed to the now banned-pesticide.
“People need to know that [obesogenic effects] are going on,” Lustig said. “Because it affects not just them, but their unborn children. This problem’s going to affect generation after generation until we get a hold of it.”
Cause and effect
Directly proving a causal link between a hazard and a human health impact is difficult for the simple reason that it is not ethical to perform harmful experiments on people. But strong epidemiological evidence can stack up to a level equivalent to proof, such as with tobacco smoking and lung cancer.
Lustig said that point had been reached for obesogens, 16 years after the term was first coined. “We’ll never have randomised control trials – they would be illegal and unethical. But we now have the proof for obesogens and obesity.”
The obesogen paradigm has not been taken up by mainstream researchers so far. But Prof Barbara Corkey, at Boston University School of Medicine and past president of the Obesity Society, said: “The initial worldview was that obesity is caused by eating too much and exercising too little. And this is nonsense.
“It’s not the explanation because all of the creatures on Earth, including humans, eat when they’re hungry and stop when they are full. Every cell in the body knows if you have enough food,” she said. “Something has disrupted that normal sensing apparatus and it is not volition.
“People who are overweight and obese go to tremendous extremes to lose weight and the diet industry has fared extremely well,” Corky said. “We’ve learned that doesn’t work. When the medical profession doesn’t understand something, we always blame patients and unfortunately, people are still being held responsible for [obesity].”
Lustig said: “Gluttony and sloth are just the outward manifestations of these biochemical perturbations that are going on beneath the surface.”
Super-sized
How much of the obesity pandemic may be caused by obesogens is not known, though Heindel said they will have an “important role”.
Lustig said: “If I had to guess, based on all the work and reading I’ve done, I would say obesogens will account for about 15% to 20% of the obesity epidemic. But that’s a lot.” The rest he attributes to processed food diets, which themselves contain some obesogens.
“Fructose is a primary driver of a lot of this,” he said. “It partitions energy to fat in the liver and is a prime obesogen. Fructose would cause obesity even if it didn’t have calories.” A small 2021 trial found that an ultra-processed diet caused more weight gain than an unprocessed diet, despite containing the same calories in the meals offered to participants.
Cutting exposure to obesogens is difficult, given that there are now 350,000 synthetic chemicals, many of which are pervasive in the environment. But those known to be harmful can be removed from sale, as is happening in Europe.
Heindel said prospective mothers in particular could adjust what they eat and monitor what their children play with in their early years: “Studies have shown modifying diets can within a week or so cause a significant drop in several obesogens.”
Lustig said: “This cause is very pervasive and pernicious, and it’s also lucrative to a lot of [chemical] companies. But we must address it rationally.” To do that, the “knowledge gap” among doctors, regulators and policymakers must be addressed, the scientists said.
“It’s time now that [obesity researchers and clinicians] should start paying attention and, if they don’t think the data is strong enough, tell us what more to do,” said Heindel, who is organising a conference to tackle this issue.
Corkey is yet to be fully convinced by the obesogen paradigm, but said the concept of an environmental toxin is probably the right direction to go in. “Is there proof? No, there is not,” she said. “It’s a very difficult problem, because the number of chemicals in our environment has just astronomically increased.
“But there’s no alternative hypothesis that to me makes any sense and I would certainly challenge anyone who has a better, testable idea to come forth with it,” she said. “Because this is a serious problem that is impacting our societies enormously, especially children. The problems are getting worse, not better – we’re going in the wrong direction as it stands.”
• This article was amended on 20 May 2022. An earlier version referred to a small 2021 trial that found an ultra-processed diet caused more weight gain than an unprocessed diet, and said that both diets contained the same calories. To clarify: the meals offered for both diets contained the same calories, but participants could choose how much of each meal they consumed.
